Trauma-induced alterations in macrophage function.
BACKGROUND
The juxtaposition of immune suppression and a hyperactive inflammatory response after injury represents a paradox in immune function. The aim of this study was to evaluate the delayed macrophage hypersecretion of inflammatory mediators in relation to functional macrophage defects.


METHODS
BALB/c mice were randomized to control or trauma (femur fracture plus 40% blood volume hemorrhage) groups. One and 7 days after injury, splenic macrophages were isolated and assayed for antigen presentation and the production of inflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, prostaglandin E2, H2O2, and nitric oxide.


RESULTS
One day after injury, there were significantly diminished macrophage antigen presentation and decreased mean production of TNF-alpha, IL-6, and H2O2. In contrast, 7 days after injury, splenic macrophages produced significantly increased mean amounts of TNF-alpha, IL-6, prostaglandin E2, H2O2, and nitric oxide, with a persistent functional defect in antigen presentation.


CONCLUSIONS
This phasic response to trauma suggests a persistent state of macrophage dysregulation that may help explain the paradox of immune suppression, manifested by functional defects predisposing patients to increased infections, in the setting of inflammatory mediator hypersecretion, predisposing patients to the systemic inflammatory response syndrome/multiple organ dysfunction syndrome.
McCarter
M D
MD
Department of Surgery, New York Hospital-Cornell University Medical College, NY 10021, USA.
Mack
V E
VE
Daly
J M
JM
Naama
H A
HA
Calvano
S E
SE
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005264:Femoral Fractures; D006470:Hemorrhage; D006861:Hydrogen Peroxide / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000276:immunology*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D015232:Dinoprostone